Djanggan Sargowo

Vasa vasorum anti-angiogenesis through H2O2, HIF-1α, NF-κB, and iNOS inhibition by mangosteen pericarp ethanolic extract (Garcinia mangostana Linn) in hypercholesterol-diet-given Rattus norvegicus Wistar strain

Background Oxidative stress in atherosclerosis produces H2O2 and triggers the activation of nuclear factor kappa beta (NF-κB) and increase of inducible nitric oxide synthase (iNOS). The formation of vasa vasorum occurs in atherosclerosis. Vasa vasorum angiogenesis is mediated by VEGFR-1 and upregulated by hypoxia-inducible factor-1α (HIF-1α). The newly formed vasa vasorum are fragile and immature and thus increase plaque instability. It is necessary to control vasa vasorum angiogenesis by using mangosteen pericarp antioxidant. This study aims to demonstrate that mangosteen pericarp ethanolic extract can act as vasa vasorum anti-angiogenesis through H2O2, HIF-1α, NF-κB, and iNOS inhibition in rats given a hypercholesterol diet. Methods This was a true experimental laboratory, in vivo posttest with control group design, with 20 Rattus norvegicus Wistar strain rats divided into five groups (normal group, hypercholesterol group, and hypercholesterol groups with certain doses of mangosteen pericarp ethanolic extract: 200, 400, and 800 mg/kg body weight). The parameters of this study were H2O2 measured by using colorimetric analysis, as well as NF-κB, iNOS, and HIF-1α, which were measured by using immunofluorescence double staining and observed with a confocal laser scanning microscope in aortic smooth muscle cell. The angiogenesis of vasa vasorum was quantified from VEGFR-1 level in aortic tissue and confirmed with hematoxylin and eosin staining. Results Analysis of variance test and Pearson’s correlation coefficient showed mangosteen pericarp ethanolic extract had a significant effect (P<0.05) in decreasing vasa vasorum angiogenesis through H2O2, HIF-1α, NF-κB, and iNOS inhibition in hypercholesterol-diet-given R. norvegicus Wistar strain. Conclusion Mangosteen pericarp ethanolic extract 800 mg/kg body weight is proven to decrease vasa vasorum angiogenesis. Similar studies with other inflammatory parameters are encouraged to clarify the mechanism of vasa vasorum angiogenesis inhibition by mangosteen pericarp ethanolic extract.

Lowering Inflammation Level by Lp-PLA2 Inhibitor (Darapladib) in Early Atherosclerosis Development: in vivo Rat Type 2 Diabetes Mellitus Model

Background: The etiology of the ventricular dilation and dysfunction that occurs in idiopathic dilated cardiomyopathy (DCM) is unknown. Aim: The present study was aimed to study clinical characteristics of the patients admitted with idiopathic DCM and compare them with healthy controls. Methods: Thirty newly diagnosed patients with DCM and 30 healthy control were enrolled from Cardiology OPD, PGIMER, Chandigarh from Jan 2011 to Jun 2012. Patients with heart failure secondary to idiopathic DCM of age >18 years were included if they were willing, provide written informed consent and does not meet any of the exclusion criteria. Idiopathic DCM was diagnosed by the presence of left ventricular dilatation and systolic dysfunction (LVEF Results: Mean age of idiopathic DCM patients and control was 48.37±10.82 years and 49.2±9.27 (P=0.75) respectively. There were more males (66.7%) than females (33.3%) in the patient group. It was observed that the treatment with beta blockers, furosemide, spironolactone, ACE inhibitors, and ARBs significantly improved ejection fraction (EF) (P=0.000), and LVES (P=0.000). Conclusion: In our study, treatment with the medications significantly improved EF and LVES. However, there was no treatment-based difference in the patients on ACE inhibitors or ARBs in the improvement in EF. Our study also observed significance difference in platelets count, SGOT, SGPT, and LDL levels in idiopathic DCM patients when compared with healthy controls. Key words: DCM, LVEF, LVES, NYHA Class, ACE Inhibitors, ARBs

Modulation of paraoxonase activity (PON)-1 by xanthone in sub chronic exposure of orgnophosphate: Antioxidant in dichorvos intoxicity

This research aims to find out the levels of xanthone in mangosteen pericarp extract (MPE) and to prove the ability of xanthone in modulating the activity of paraoxonase-1 (PON-1), reduce oxidized-low density lipoprotein (ox-LDL) and increase the levels of acetylcholinesterase (AChE) serum in animal model with organophosphat subchronic and subcutaneous exposure. This research is a true experimental laboratory with in vivo approach to post-test with control group, using 25 animal models of Wistar strain of Rattus novergicus, were exposed to dichlorvos as organophosphates (2 mg/kgBW/day) for 21 days. Those animal models are divided into no exposure group, organophosphate exposure group, and organophosphate exposure plus administration of xanthone groups. The parameters (levels of PON-1, ox-LDL and AChE measured by ELISA Test. The results showed that administration of xanthone significantly increased the levels of AChE, decreased levels of ox-LDL and PON-1.

Ganoderma Lucidum Subchronic Toxicity on The Liver As Anti-oxidant and Anti-inflamatory Agent for Cardivascular Disease

Background: Gonoderma lucidum is claimed to have beneficial health effects, and is developing into a comprehensive form of treatment against cardiovascular disease. Previous studies have successfully proven Ganoderma lucidum polysaccharides peptide ability as an antioxidant and anti-inflammatory agent whereby reducing levels of MDA, hs-CRP, H2O2, total cholesterol, foam cells as well as increasing the levels of HDL in experimental testing using Wistar rat (Rattus norvegicus strain wistar) fed with a high-fat diet. In order to develop Gonaderma lucidum polysaccharides peptide as an integral and comprehensive form of treatment against cardiovascular disease, further research regarding the subchronic toxicity on the liver was performed. Objective: To determine the safety profile of liver function in the use of Ganoderma lucidum polysaccharides peptide through subchronic toxicity studies on experimental animals. Method: The study of subchronic Ganoderma lucidum toxicity was performed using Wistar rat (Rattus novergicus strain wistar). 6 rats/sex/group were given a pure, freeze dried solution of Ganoderma lucidum with dosage ranging from 0,300, 600, 1200 mg/per kg body weight administered via gavage once a day for 90 days. Result : 90 days after the administration of pure, freeze dried Ganoderma lucidum solution with dosages ranging from 300 mg–1200 mg/per kg body weight, there were no observable toxic symptoms in male and female rats. There was no adverse effect on liver function with the administration of the maximum dosage (1200 mg/ per kg body weight). Gross pathology examinations of the rats liver after the maximal dosage of Ganoderma lucidum extract proved to be unremarkable. These findings are supported by the results of clinical pathology and histopathology of liver cells which do not indicate a change in morphology and histopathology of the liver. Conclusion: The result of this study shows that oral administration of Ganoderma lucidum polysaccharides peptide until the maximum dose of 1200 mg/per kg body weight/day does not cause toxic effects in the liver.

6 THE ROLE OF PRIMARY PREVENTION AGAINST REDUCING HYPERTENSION FOCUS ON SUBJECTS WITH HIGH TOTAL CHOLESTEROL AND HIGH TRIGLYCERIDES IN BUMIAJI VILLAGE, BATU, EAST JAVA

Background: Hypertension becomes a disease that keeps on increasing. In 2016 the National Health Indicator Survey saw the number of hypertension rise to 32.4 percent. Many factors contributes to hypertension one of them is lipid disorders. Dyslipidaemia, a strong predictor of cardiovascular disease, causes endothelial damage which leads to increased blood pressure. The number of farmers in Batu is 19,258 people, and in Bumiaji Village has the highest numbers of farmers than other sub-districts, which is about 45% of the total farmers in Batu (Census of Agriculture, 2013). Objectives: The aim of this study was to evaluate the efficacy of population based intervention in improving knowledge and physical activity for reducing blood pressure and dyslipidemia in population of farmers in Bumiaji Village, Batu. Methods: This study was an interventional analytic study involving 102 subjects from Bumiaji Village, Batu. All participants were given the same intervention for 3 months. Blood test for total cholesterol, triglycerides and vital signs were performed in all subjects before and after intervention. Subjects did heart exercise in 60 minutes with frequency two times a week in 3 months and received training sessions about hypertension, diabetes mellitus, obesity, smoking, and nutrition balance. From the data, we took 22 subjects with hypertension, high total cholesterol and high triglycerides. We analysed the data using Wilcoxon Signed Ranks Test to evaluate pre and post intervention of Blood Pressure (BP). Results: From our study, it was found that after the intervention, there were 17 people who experienced a decrease in systolic blood pressure, and 5 others had the same results as pre-intervention. There were 13 people who experienced a decrease in diastolic blood pressure, and 9 others had the same results as pre-intervention. The mean value for systolic blood pressure before intervention is 134 ± 17,32, diastolic blood pressure pre-intervention 88.23 ± 12.09 systolic blood pressure after intervention is 124,09 ± 11.82 and diastolic blood pressure after intervention is 82.27 ± 9.73. The mean value for total cholesterol before intervention is 224.14 ± 26.08, triglycerides pre intervention 209.82 ± 13.02, total cholesterol after intervention is 208.82 ± 35.64 and triglyceride after intervention is 181.09 ± 110.15. Conclusions: Primary prevention for subjects with hypertension, high total cholesterol and high triglycerides has tendency of lowering the value of blood pressure, total cholesterol and triglycerides.

Atheroprotective effect of the Agaricus blazei Mur ill extract in High Fat Diet-Induced Mice

The purpose of the present study was to provide evidence of the potential of Agaricus blazei Murill extract as atheroprotective agent. The study was conducted with 25 male mice (Mus musculus) divided into f ive groups consisting of f ive mice in each group. Three doses of Agaricus blazei Murill extract: D1 (100 mg/kg body weight), D2 (200 mg/kg body weight), and D3 (400 mg/kg body weight) was used. All treatment groups, except for normal mice were induced to high fat diet (HFD) and given A. blazei extract for 12 weeks. The activation of T regulatory cells, the production of anti-inflammatory cytokines TGF-?, and the number of LpPLA2-expressing cells in spleen were analyzed using flow cytometry. Results showed that administration of A. blazei extract was able to induce activation of T regulatory cells, increased the production of anti-inflammatory cytokines TGF-β, and decreased the number of LpPLA2-expressing cells in the spleen signif icantly. Our results revealed that A. blazei extract is a good candidate as atheroprotective agent by reducing inflammation in atheroschlerosis.

The role of polysaccharide peptide of Ganoderma lucidum as a potent antioxidant against atherosclerosis in high risk and stable angina patients

Objectives Antioxidants can reduce oxidative radicals that affect the early phase of atherogenesis, that is endothelial dysfunction. Polysaccharide Peptide (PsP) derived from Ganoderma lucidum has an active substance in the form of β-glucan. Previous studies have proven the PsP of Ganoderma lucidum as an effective antioxidant in atherosclerotic rats and shows no toxicity in animal model. This study aims to prove the effect of PsP as potent antioxidant in high risk and stable angina patients. Method This is a clinical trial conducted to 37 high risk and 34 stable angina patients, which were determined based on ESC Stable CAD Guidelines and Framingham risk score, with pre and post test design without control group. The parameters are superoxide dimustase (SOD) and malondialdehyde (MDA) concentration, circulating endothelial cell (CEC) and endothelial progenitor cell (EPC) counts. The patients were given PsP 750 mg/day in 3 divided dose for 90 days. Paired t-test was performed for normally distributed data, and Wilcoxon test for not normally distributed data, and significant level of p ≤ 0,05. Results SOD level in high risk patients slightly increased but not statistically significant with p = 0,22. Level of SOD in stable angina group significantly increased with p = 0,001. MDA concentration significantly reduced in high risk and stable angina patients with p = 0.000. CEC significantly reduced both in high risk and stable angina patients, with p = 0.000 in both groups. EPC count significantly reduced in high risk and stable angina with p = 0.000. Conclusion PsP of Ganoderma lucidum is a potent antioxidant against pathogenesis of atherosclerosis in stable angina and high risk patients

OS 10-03 THE DISTINCTIVE EFFECT OF POLYSACCHARIDE PEPTIDES GANODERMA LUCIDUM AS ANTI ATHEROGENESIS IN STABLE ANGINA PATIENTS.

Objective: This study was aimed to evaluate the effects of polysaccharide peptides (PsP) of Ganoderma lucidum as anti inflammation, anti oxidant, anti diabetic and anti lipid in stable angina pectoris patients. Design and Method: This is a quasi clinical trial experimental study on 34 Stable Angina patients in Saiful Anwar General Hospital was determined based on ESC Stable CAD guidelines, with pre-test and post-test design without control. Parameter measured were TNF alfa, IL-6, MDA, SOD, HbA1c, Fasting glucose and Total cholesterol. The patients were given PsP 750 mg/day in divided dose for 90 days, while continuing the previous medications as directed by guidelines. The data was analyzed by paired t-test for parametric data and Wilcoxon test for non-parametric data. Results: After PSP administration we found significantly reduce the level of TNF alfa level from 11444 ± 2352.70 to 476.13 ± 482.99 (p = 0.000), IL-6 level from 294.70 ± 123.28 to 24.41 ± 21.45 (p = 0.000), MDA level from 95.63 ± 21.27 to 44,84 ± 50,95 (p = 0.000), increased SOD level from 3.41 ± 0,46 to 5,97 ± 4,19, HbA1c from 6.59 ± 3.05 to 5.62 ± 1.41 (p = 0.009), fasting glucose level reduced from 113.08 ± 12.44 mg/dl to 97.95 ± 6.22 mg/dl (p = 0.342) and total cholesterol level reduced from 205,49 ± 48,49 mg/dl to 182,11 ± 73,81 mg/dl (p = 0.081). Conclusions: Ganoderma lucidum polysaccharide peptides have distinctive effect on anti inflammation, anti oxidant, anti diabetic and anti lipid in stable angina pectoris and promising as additional drug in the treatment of coronary artery disease caused by atherosclerotic process.

LBPS 01–05 GANODERMA LUCIDUM POLYSACCHARIDE PEPTIDES AS ANTIOXIDANT, ANTI-INFLAMMATION, ANTI-HYPERTENSION AND ANTI-LIPID IN HIGH-RISK PATIENTS OF ATHEROSCLEROSIS

Objective: Ganoderma lucidum is a type of mushroom that has been used for thousands years throughout Asia. It is known to demonstrate numerous health benefiting properties including antioxidant, anti-inflammation, anticancer effects, hypoglycemic and blood cholesterol reducing properties. This research was conducted to determine the efficacy of Ganoderma lucidum polysaccharide peptides (PSP) as anti-inflammation and antioxidant in cardiovascular disease Design and Method: This is a prospective study with pre-test and post-test design of 37 high-risk patients of cardiovascular disease based on the Framingham Risk Score that was conducted for 3 months. Patients were advised to consume PSP 3×250 mg as an adjuvant to their previous medications. The primary endpoint was the change in cholesterol levels, blood pressure and antioxidant markers. Results: The administration of PSP 3x250 mg could reduce total cholesterol level by 3.48 ± 46.9 mg/dl (p = 0.672). Both pre- and post-test of total cholesterol are significantly correlated (r = 0.618, p = 0.000). PSP administration, however, increased the level of HDL cholesterol by 7.84 ± 10.79 (p = 0.000). The systolic blood pressure decreased from 130.14 ± 43.37 mmHg to 118.24 ± 55.68 (p = 0.109), and the diastolic blood pressure decreased from 80 ± 25.74 mmHg to 73.24 ± 33.85 mmHg (p = 0.102). Despite a great reduction of blood pressure to normal range, it was not statistically significant. The reduction of anti-inflammatory markers interleukin-6 (IL-6), from 279.75 ± 120.76 to 29.32 ± 26.44 (p = 0.000) and TNF alpha, from 13447.84 ± 2199.46 to 544.85 ± 292.06 (p = 0.000) were significant. Malondialdehyde (MDA) level also decreased significantly with PSP treatment for 3 months (p = 0.000). Conclusions: The administration of polysaccharide peptides of Ganoderma lucidum for three months in high-risk patients with hypertension can reduce the blood pressure within normal range, improve total cholesterol level and significantly play role as anti-inflammation and antioxidant in cardiovascular disease.

PS 16-11 GANODERMA LUCIDUM POLYSACCHARIDE PEPTIDES: A POTENT PROTECTIVE ENDOTHELIAL VASCULAR AND ANTI-LIPID IN ATHEROSCLEROSIS

Objective: Atherosclerosis has been known as the hallmark of cardiovascular diseases. It involves inflammation, oxidative stress and endothelial dysfunction, which stimulate cytokines and other biomarkers. Ganoderma lucidum is a mushroom that is known for its numerous pharmacological effects such as anti-tumour, immunomodulator, antioxidant, anti-diabetic and anti-lipid. This study was aimed to evaluate the effects of polysaccharide peptides (PSP) of Ganoderma lucidum on circulating endothelial cells (CECs), endothelial progenitor cells (EPCs) and nitric oxide (NO) as the hallmark of endothelial vascular injury; and TNF alpha and IL-6 as inflammatory markers. Design and method: This is a prospective study with pre- and post-test design that involves 34 patients with stable angina and 37 high-risk patients according to Framingham Risk Score and they were given PSP 750 mg/day in divided dose for 3 months as adjuvant therapy to their previous medications. The primary endpoint is the level of CEC and EPC after treatment. We also evaluate lipid profile, TNF alpha, IL-6, and NO concentrations. Results: The levels of CEC and EPC significantly reduced in stable angina patients (p = 0.000) and high-risk patients (p = 0.000). The levels of TNF alpha and IL-6 also decreased significantly after PSP administration, interestingly followed by the level of NO. Total cholesterol level reduced from 205.49 ± 48.49 mg/dl to 182.11 ± 73.81 mg/dl (p = 0.081) and LDL reduced from 126.17 ± 38.87 mg/dl to 116.17 ± 54.16 mg/dl (p = 0.268) in patients with stable angina. The same reduction also occurs in high-risk patients, where the level of total cholesterol (p = 0.193) and LDL cholesterol (p = 0.580) decreased after 3-month treatment. Conclusions: Ganoderma lucidum polysaccharide peptides have a potent protective vascular effect and anti-lipid in stable angina pectoris and promising as adjuvant therapy on the treatment of atherosclerotic cardiovascular diseases.